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Critical Care (London, England) Jan 2023Vasopressors and fluids are the cornerstones for the treatment of shock. The current international guidelines on shock recommend norepinephrine as the first-line... (Review)
Review
Vasopressors and fluids are the cornerstones for the treatment of shock. The current international guidelines on shock recommend norepinephrine as the first-line vasopressor and vasopressin as the second-line vasopressor. In clinical practice, due to drug availability, local practice variations, special settings, and ongoing research, several alternative vasoconstrictors and adjuncts are used in the absence of precise equivalent doses. Norepinephrine equivalence (NEE) is frequently used in clinical trials to overcome this heterogeneity and describe vasopressor support in a standardized manner. NEE quantifies the total amount of vasopressors, considering the potency of each such agent, which typically includes catecholamines, derivatives, and vasopressin. Intensive care studies use NEE as an eligibility criterion and also an outcome measure. On the other hand, NEE has several pitfalls which clinicians should know, important the lack of conversion of novel vasopressors such as angiotensin II and also adjuncts such as methylene blue, including a lack of high-quality data to support the equation and validate its predictive performance in all types of critical care practice. This review describes the history of NEE and suggests an updated formula incorporating novel vasopressors and adjuncts.
Topics: Humans; Norepinephrine; Shock, Septic; Shock; Vasoconstrictor Agents; Vasopressins; Critical Care
PubMed: 36670410
DOI: 10.1186/s13054-023-04322-y -
JAMA Mar 2020Vasopressors are commonly administered to intensive care unit (ICU) patients to raise blood pressure. Balancing risks and benefits of vasopressors is a challenge,... (Comparative Study)
Comparative Study Randomized Controlled Trial
IMPORTANCE
Vasopressors are commonly administered to intensive care unit (ICU) patients to raise blood pressure. Balancing risks and benefits of vasopressors is a challenge, particularly in older patients.
OBJECTIVE
To determine whether reducing exposure to vasopressors through permissive hypotension (mean arterial pressure [MAP] target, 60-65 mm Hg) reduces mortality at 90 days in ICU patients aged 65 years or older with vasodilatory hypotension.
DESIGN, SETTING, AND PARTICIPANTS
A multicenter, pragmatic, randomized clinical trial was conducted in 65 ICUs in the United Kingdom and included 2600 randomized patients aged 65 years or older with vasodilatory hypotension (assessed by treating clinician). The study was conducted from July 2017 to March 2019, and follow-up was completed in August 2019.
INTERVENTIONS
Patients were randomized 1:1 to vasopressors guided either by MAP target (60-65 mm Hg, permissive hypotension) (n = 1291) or according to usual care (at the discretion of treating clinicians) (n = 1307).
MAIN OUTCOME AND MEASURES
The primary clinical outcome was all-cause mortality at 90 days.
RESULTS
Of 2600 randomized patients, after removal of those who declined or had withdrawn consent, 2463 (95%) were included in the analysis of the primary outcome (mean [SD] age 75 years [7 years]; 1387 [57%] men). Patients randomized to the permissive hypotension group had lower exposure to vasopressors compared with those in the usual care group (median duration 33 hours vs 38 hours; difference in medians, -5.0; 95% CI, -7.8 to -2.2 hours; total dose in norepinephrine equivalents median, 17.7 mg vs 26.4 mg; difference in medians, -8.7 mg; 95% CI, -12.8 to -4.6 mg). At 90 days, 500 of 1221 (41.0%) in the permissive hypotension compared with 544 of 1242 (43.8%) in the usual care group had died (absolute risk difference, -2.85%; 95% CI, -6.75 to 1.05; P = .15) (unadjusted relative risk, 0.93; 95% CI, 0.85-1.03). When adjusted for prespecified baseline variables, the odds ratio for 90-day mortality was 0.82 (95% CI, 0.68 to 0.98). Serious adverse events were reported for 79 patients (6.2%) in the permissive care group and 75 patients (5.8%) in the usual care group. The most common serious adverse events were acute renal failure (41 [3.2%] vs 33 [2.5%]) and supraventricular cardiac arrhythmia (12 [0.9%] vs 13 [1.0%]).
CONCLUSIONS AND RELEVANCE
Among patients 65 years or older receiving vasopressors for vasodilatory hypotension, permissive hypotension compared with usual care did not result in a statistically significant reduction in mortality at 90 days. However, the confidence interval around the point estimate for the primary outcome should be considered when interpreting the clinical importance of the study.
TRIAL REGISTRATION
isrctn.org Identifier: ISRCTN10580502.
Topics: Acute Kidney Injury; Aged; Aged, 80 and over; Atrial Premature Complexes; Cognition Disorders; Confidence Intervals; Female; Hospital Mortality; Humans; Hypotension; Intensive Care Units; Kaplan-Meier Estimate; Male; Vasoconstrictor Agents
PubMed: 32049269
DOI: 10.1001/jama.2020.0930 -
Archives of Disease in Childhood. Fetal... Jul 2021In persistent pulmonary hypertension of the newborn (PPHN), the ratio of pulmonary vascular resistance to systemic vascular resistance is increased. Extrapulmonary... (Review)
Review
In persistent pulmonary hypertension of the newborn (PPHN), the ratio of pulmonary vascular resistance to systemic vascular resistance is increased. Extrapulmonary shunts (patent ductus arteriosus and patent foramen value) allow for right-to-left shunting and hypoxaemia. Systemic hypotension can occur in newborns with PPHN due to variety of reasons, such as enhanced peripheral vasodilation, impaired left ventricular function and decreased preload. Systemic hypotension can lead to end organ injury from poor perfusion and hypoxaemia in the newborn with PPHN. Thus, it must be managed swiftly. However, not all newborns with PPHN and systemic hypotension can be managed the same way. Individualised approach based on physiology and echocardiographic findings are necessary to improve perfusion to essential organs. Here we present a review of the physiology and mechanisms of systemic hypotension in PPHN, which can then guide treatment.
Topics: Blood Pressure Monitors; Extracorporeal Membrane Oxygenation; Fluid Therapy; Hemodynamics; Humans; Hypotension; Infant, Newborn; Persistent Fetal Circulation Syndrome; Practice Guidelines as Topic; Vasoconstrictor Agents
PubMed: 33478959
DOI: 10.1136/archdischild-2020-319705 -
Seminars in Respiratory and Critical... Oct 2021Corticosteroids have been used for decades in the adjunctive treatment of severe infections in intensive care. The most frequent scenario in intensive care is in septic... (Review)
Review
Corticosteroids have been used for decades in the adjunctive treatment of severe infections in intensive care. The most frequent scenario in intensive care is in septic shock, where low doses of glucocorticoids appear to restore vascular responsiveness to norepinephrine. There is a strong body of evidence suggesting that hydrocortisone reduces time on vasopressor, and may modulate the immune response. In this review, we explore the current evidence supporting the use of corticosteroids in septic shock, its benefits, and potential harms. In addition to landmark clinical trials, we will also describe new frontiers for the use of corticosteroids in septic shock which should be explored in future studies.
Topics: Adrenal Cortex Hormones; Glucocorticoids; Humans; Hydrocortisone; Shock, Septic; Vasoconstrictor Agents
PubMed: 34544190
DOI: 10.1055/s-0041-1733900 -
Journal of Critical Care Feb 2021Calculating equipotent doses between vasopressor agents is necessary in clinical practice and research pertaining to the management of shock. This scoping review... (Review)
Review
PURPOSE
Calculating equipotent doses between vasopressor agents is necessary in clinical practice and research pertaining to the management of shock. This scoping review summarizes conversion ratios between vasopressors and provides a formula to incorporate into study designs.
MATERIALS AND METHODS
Medline, Embase and Web of Science databases were searched from inception to 21st October 2020. Additional papers were obtained through bibliography searches of retrieved articles. Two investigators assessed articles for eligibility. Clinical trials comparing the potency of at least two intravenous vasopressors (norepinephrine, epinephrine, dopamine, phenylephrine, vasopressin, metaraminol or angiotensin II), with regard to an outcome of blood pressure, were selected.
RESULTS
Of 16,315 articles, 21 were included for synthesis. The range of conversion ratios equivalent to one unit of norepinephrine were: epinephrine (0.7-1.4), dopamine (75.2-144.4), metaraminol (8.3), phenylephrine (1.1-16.3), vasopressin (0.3-0.4) and angiotensin II (0.07-0.13). The following formula may be considered for the calculation of norepinephrine equivalents (NE) (all in mcg/kg/min, except vasopressin in units/min): NE = norepinephrine + epinephrine + phenylephrine/10 + dopamine/100 + metaraminol/8 + vasopressin*2.5 + angiotensin II*10.
CONCLUSION
A summary of equipotent ratios for common vasopressors used in clinical practice has been provided. Our formula may be considered to calculate NE for studies in the intensive care unit.
Topics: Epinephrine; Humans; Norepinephrine; Phenylephrine; Shock; Vasoconstrictor Agents
PubMed: 33220576
DOI: 10.1016/j.jcrc.2020.11.002 -
Critical Care (London, England) Jul 2020Measurement of central venous pressure (CVP) can be a useful clinical tool. However, the formal utility of CVP measurement in preventing mortality in septic patients has...
PURPOSE
Measurement of central venous pressure (CVP) can be a useful clinical tool. However, the formal utility of CVP measurement in preventing mortality in septic patients has never been proven.
METHODS
The Medical Information Mart for Intensive Care III (MIMIC-III) database was searched to identify septic patients with and without CVP measurements. The primary outcome was 28-day mortality. Multivariate regression was used to elucidate the relationship between CVP measurement and 28-day mortality, and propensity score matching (PSM) and an inverse probability of treatment weighing (IPTW) were employed to validate our findings.
RESULTS
A total of 10,275 patients were included in our study, of which 4516 patients (44%) underwent CVP measurement within 24 h of intensive care unit (ICU) admission. The risk of 28-day mortality was reduced in the CVP group (OR 0.60 (95% CI 0.51-0.70; p < 0.001)). Patients in the CVP group received more fluid on day 1 and had a shorter duration of mechanical ventilation and vasopressor use, and the reduction in serum lactate was greater than that in the no CVP group. The mediating effect of serum lactate reduction was significant for the whole cohort (p = 0.04 for the average causal mediation effect (ACME)) and patients in the CVP group with an initial CVP level below 8 mmHg (p = 0.04 for the ACME).
CONCLUSION
CVP measurement was associated with decreased risk-adjusted 28-day mortality among patients with sepsis and was proportionally mediated through serum lactate reduction.
Topics: Aged; Aged, 80 and over; Central Venous Pressure; Cohort Studies; Databases, Factual; Female; Fluid Therapy; Humans; Intensive Care Units; Male; Middle Aged; Monitoring, Physiologic; Outcome Assessment, Health Care; Prognosis; Retrospective Studies; Sepsis; Vasoconstrictor Agents
PubMed: 32665010
DOI: 10.1186/s13054-020-03109-9 -
Anesthesia and Analgesia Oct 2022Cardiac surgery-associated acute kidney injury (CS-AKI) is common and is associated with increased risk for postoperative morbidity and mortality. Our recent survey of... (Meta-Analysis)
Meta-Analysis Review
Cardiac surgery-associated acute kidney injury (CS-AKI) is common and is associated with increased risk for postoperative morbidity and mortality. Our recent survey of the Society of Cardiovascular Anesthesiologists (SCA) membership showed 6 potentially renoprotective strategies for which clinicians would most value an evidence-based review (ie, intraoperative target blood pressure, choice of specific vasopressor agent, erythrocyte transfusion threshold, use of alpha-2 agonists, goal-directed oxygen delivery on cardiopulmonary bypass [CPB], and the "Kidney Disease Improving Global Outcomes [KDIGO] bundle of care"). Thus, the SCA's Continuing Practice Improvement Acute Kidney Injury Working Group aimed to provide a practice update for each of these strategies in cardiac surgical patients based on the evidence from randomized controlled trials (RCTs). PubMed, EMBASE, and Cochrane library databases were comprehensively searched for eligible studies from inception through February 2021, with search results updated in August 2021. A total of 15 RCTs investigating the effects of the above-mentioned strategies on CS-AKI were included for meta-analysis. For each strategy, the level of evidence was assessed using the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) methodology. Across the 6 potentially renoprotective strategies evaluated, current evidence for their use was rated as "moderate," "low," or "very low." Based on eligible RCTs, our analysis suggested using goal-directed oxygen delivery on CPB and the "KDIGO bundle of care" in high-risk patients to prevent CS-AKI (moderate level of GRADE evidence). Our results suggested considering the use of vasopressin in vasoplegic shock patients to reduce CS-AKI (low level of GRADE evidence). The decision to use a restrictive versus liberal strategy for perioperative red cell transfusion should not be based on concerns for renal protection (a moderate level of GRADE evidence). In addition, targeting a higher mean arterial pressure during CPB, perioperative use of dopamine, and use of dexmedetomidine did not reduce CS-AKI (a low or very low level of GRADE evidence). This review will help clinicians provide evidence-based care, targeting improved renal outcomes in adult patients undergoing cardiac surgery.
Topics: Acute Kidney Injury; Adult; Anesthesiologists; Cardiac Surgical Procedures; Dexmedetomidine; Dopamine; Humans; Oxygen; Vasoconstrictor Agents
PubMed: 35544772
DOI: 10.1213/ANE.0000000000006068 -
Critical Care (London, England) Aug 2023During septic shock, vasopressor infusion is usually started only after having corrected the hypovolaemic component of circulatory failure, even in the most severe...
During septic shock, vasopressor infusion is usually started only after having corrected the hypovolaemic component of circulatory failure, even in the most severe patients. However, earlier administration of norepinephrine, simultaneously with fluid resuscitation, should be considered in some cases. Duration and depth of hypotension strongly worsen outcomes in septic shock patients. However, the response of arterial pressure to volume expansion is inconstant, delayed, and transitory. In the case of profound, life-threatening hypotension, relying only on fluids to restore blood pressure may unduly prolong hypotension and organ hypoperfusion. Conversely, norepinephrine rapidly increases and better stabilizes arterial pressure. By binding venous adrenergic receptors, it transforms part of the unstressed blood volume into stressed blood volume. It increases the mean systemic filling pressure and increases the fluid-induced increase in mean systemic filling pressure, as observed in septic shock patients. This may improve end-organ perfusion, as shown by some animal studies. Two observational studies comparing early vs. later administration of norepinephrine in septic shock patients using a propensity score showed that early administration reduced the administered fluid volume and day-28 mortality. Conversely, in another propensity score-based study, norepinephrine administration within the first hour following shock diagnosis increased day-28 mortality. The only randomized controlled study that compared the early administration of norepinephrine alone to a placebo showed that the early continuous administration of norepinephrine at a fixed dose of 0.05 µg/kg/min, with norepinephrine added in open label, showed that shock control was achieved more often than in the placebo group. The choice of starting norepinephrine administration early should be adapted to the patient's condition. Logically, it should first be addressed to patients with profound hypotension, when the arterial tone is very low, as suggested by a low diastolic blood pressure (e.g. ≤ 40 mmHg), or by a high diastolic shock index (heart rate/diastolic blood pressure) (e.g. ≥ 3). Early administration of norepinephrine should also be considered in patients in whom fluid accumulation is likely to occur or in whom fluid accumulation would be particularly deleterious (in case of acute respiratory distress syndrome or intra-abdominal hypertension for example).
Topics: Animals; Blood Pressure; Hypotension; Norepinephrine; Shock, Septic; Vasoconstrictor Agents; Humans
PubMed: 37608327
DOI: 10.1186/s13054-023-04593-5 -
Clinics in Liver Disease May 2022Hepatorenal syndrome (HRS) is defined as a functional renal failure without major histologic changes in individuals with severe liver disease and it is associated with a... (Review)
Review
Hepatorenal syndrome (HRS) is defined as a functional renal failure without major histologic changes in individuals with severe liver disease and it is associated with a high mortality rate. Renal hypoperfusion due to marked vasoconstriction as a result of complex circulatory dysfunction has been suggested to be the cornerstone of HRS. Splanchnic and peripheral arterial vasodilation and cirrhotic cardiomyopathy result in effective arterial hypovolemia and compensatory activation of vasoconstrictor mechanisms. The efficacy of current therapeutic strategies targeting this circulatory dysfunction is limited. Increasing evidence suggests a substantial role of systemic inflammation in HRS via either vascular or direct renal effects. Here we summarize the current understanding of HRS pathophysiology.
Topics: Female; Hepatorenal Syndrome; Humans; Liver Cirrhosis; Male; Vasoconstrictor Agents; Vasodilation
PubMed: 35487603
DOI: 10.1016/j.cld.2022.01.013 -
Critical Care Medicine Jan 2020
Topics: Critical Care; Critical Illness; Enteral Nutrition; Humans; Practice Guidelines as Topic; Vasoconstrictor Agents
PubMed: 31414992
DOI: 10.1097/CCM.0000000000003965